Quality by design

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Quality by design (QbD) is a concept first outlined by quality expert Joseph M. Juran in publications, most notably Juran on Quality by Design. [1] Designing for quality and innovation is one of the three universal processes of the Juran Trilogy, in which Juran describes what is required to achieve breakthroughs in new products, services, and processes. [2] Juran believed that quality could be planned, and that most quality crises and problems relate to the way in which quality was planned.

Contents

While quality by design principles have been used to advance product and process quality in industry, and particularly the automotive industry, they have also been adopted by the U.S. Food and Drug Administration (FDA) for the discovery, development, and manufacture of drugs. [3] [4] [5] [6]

Juran on quality by design

The Juran Trilogy [2] defines the word "quality" as having two meanings: first, the presence of features that create customer satisfaction; second, the reliability of those features. Failures in features create dissatisfactions, so removing failures is the purpose of quality improvement, while creating features is the purpose of quality by design. [7] Juran's process seeks to create features in response to understanding customer needs. These are customer-driven features. The sum of all features is the new product, service, or process. [8]

The quality by design model consists of the following steps:

  1. Establish the project design targets and goals.
  2. Define the market and customers that will be targeted.
  3. Discover the market, customers, and societal needs.
  4. Develop the features of the new design that will meet the needs.
  5. Develop or redevelop the processes to produce the features.
  6. Develop process controls to be able to transfer the new designs to operations. [7]

It is not a statistical design method like Design for Six Sigma.

Integrated planning

Integrated planning requires a team with a leader whose sole accountability is for the total success of the new product from defining the opportunity through customer purchase, use, service, and recommendation to others. This team leader reports directly to a senior executive, or the team leader can be a senior executive. Each team member's job is to ensure the success of the new product. [9] In addition to organizational integration, a successful team must begin with clearly articulated common goals for the product that are measurable and authorized by the enterprise. These goals must, at a minimum, cover such elements as:

The team will follow a structured process. The structure is the common framework for all participants in launching the new product and helps ensure success. [9]

Customer-focused optimization

Quality by design starts and ends with the customer. [1] Every new product introduction has some amount of trade-off involved. If there are multiple customers, they may have conflicting needs. Even the same customer may have needs that compete with each other. Capacity and speed compete with cost of operation. Capacity can compete with speed. Flexibility and feature-rich offerings may have reduced ease of use, and so on. [7]

Quality by design offers a range of tools and methods intended to make these tradeoffs explicit and optimal for the customer. Some tools are highly mathematical, and others relate more to customer behavior. Quality by design sets strong expectations for creative approaches to functional design, product features and goals, and production design. [10]

Control over variation and transfer to operations

Quality by design incorporates modern tools to preemptively control variation. These tools and methods begin by measuring and understanding the variation that exists by using historical data, testing, and modeling to help forecast, analyze, and eliminate the deleterious effects of variation using standard statistical techniques. [10] Process control consists of three basic activities:

  1. Evaluate the actual performance of the process
  2. Compare actual performance with goals
  3. Take action on the difference [7]

The final activity of the quality by design process is to implement the plan and validate that the transfer has occurred. [7]

Pharmaceutical quality by design

The FDA imperative is outlined in its report "Pharmaceutical Quality for the 21st Century: A Risk-Based Approach." [11] In the past few years, the agency has implemented the concepts of QbD into its pre-market processes. The focus of this concept is that quality should be built into a product with an understanding of the product and process by which it is developed and manufactured along with a knowledge of the risks involved in manufacturing the product and how best to mitigate those risks. This is a successor to the "quality by QC" (or "quality after design") approach that the companies have taken up until the 1990s. [12]

The QbD initiative, which originated from the Office of Biotechnology Products (OBP), attempts to provide guidance on pharmaceutical development to facilitate design of products and processes that maximizes the product's efficacy and safety profile while enhancing product manufacturability.

QbD activities within FDA

The following activities are guiding the implementation of QbD:

While QbD will provide better design predictions, there is also a recognition that industrial scale-up and commercial manufacturing experience provides knowledge about the process and the raw materials used therein. FDA's release of the Process Validation [12] guidance in January 2011 notes the need for companies to continue benefiting from knowledge gained, and continually improve throughout the process lifecycle by making adaptations to assure root causes of manufacturing problems are corrected.

ICH activities

Working with regulators in the European Union (the European Medicines Agency) and Japan, the FDA has furthered quality by design objectives through the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. The ICH Guidelines Q8 through Q11 encapsulate these unified recommendations and provide some assistance for manufacturers to implement quality by design into their own operations. ICH Guideline Q8 describes QbD-based drug formulation development and was first published in 2004, being subsequently revised in 2008 (Q8(R2)). [15] The ICH Guideline Q9 describes Quality Risk Management plans, [16] Q10 explains Pharmaceutical Quality Systems, [17] and Q11 refer to the development of active pharmacological substances including biologicals. [18]

In November 2017, the ICH issued Guideline Q12 for public consultation to extend the recommendations for the Product Lifecycle Management Plan that were initially defined in the Guideline Q10. [19] According to the ICH, Guideline Q13 will extend the previous guidelines to accommodate continuous pharmaceutical manufacturing [20] and Q2 (Analytical Validation) will be revised and extended into the guideline Q2(R2)/Q14 to include Analytical quality by design or AQbD. [21]

The ICH Steering Committee meets twice a year to discuss the progress of its efforts. This practical input should help ensure that quality risk management and knowledge management are used to make lifecycle adaptations that maintain process control and product quality.

See also

Further reading

Related Research Articles

A quality management system (QMS) is a collection of business processes focused on consistently meeting customer requirements and enhancing their satisfaction. It is aligned with an organization's purpose and strategic direction. It is expressed as the organizational goals and aspirations, policies, processes, documented information, and resources needed to implement and maintain it. Early quality management systems emphasized predictable outcomes of an industrial product production line, using simple statistics and random sampling. By the 20th century, labor inputs were typically the most costly inputs in most industrialized societies, so focus shifted to team cooperation and dynamics, especially the early signaling of problems via a continual improvement cycle. In the 21st century, QMS has tended to converge with sustainability and transparency initiatives, as both investor and customer satisfaction and perceived quality are increasingly tied to these factors. Of QMS regimes, the ISO 9000 family of standards is probably the most widely implemented worldwide – the ISO 19011 audit regime applies to both and deals with quality and sustainability and their integration.

<span class="mw-page-title-main">Good manufacturing practice</span> Manufacturing quality standards

Current good manufacturing practices (cGMP) are those conforming to the guidelines recommended by relevant agencies. Those agencies control the authorization and licensing of the manufacture and sale of food and beverages, cosmetics, pharmaceutical products, dietary supplements, and medical devices. These guidelines provide minimum requirements that a manufacturer must meet to assure that their products are consistently high in quality, from batch to batch, for their intended use. The rules that govern each industry may differ significantly; however, the main purpose of GMP is always to prevent harm from occurring to the end user. Additional tenets include ensuring the end product is free from contamination, that it is consistent in its manufacture, that its manufacture has been well documented, that personnel are well trained, and that the product has been checked for quality more than just at the end phase. GMP is typically ensured through the effective use of a quality management system (QMS).

GxP is a general abbreviation for the "good practice" quality guidelines and regulations. The "x" stands for the various fields, including the pharmaceutical and food industries, for example good agricultural practice, or GAP.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an initiative that brings together regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of pharmaceutical product development and registration. The mission of the ICH is to promote public health by achieving greater harmonisation through the development of technical Guidelines and requirements for pharmaceutical product registration.

An approved drug is a medicinal preparation that has been validated for a therapeutic use by a ruling authority of a government. This process is usually specific by country, unless specified otherwise.

Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages. In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results. The desired results are established in terms of specifications for outcome of the process. Qualification of systems and equipment is therefore a part of the process of validation. Validation is a requirement of food, drug and pharmaceutical regulating agencies such as the US FDA and their good manufacturing practices guidelines. Since a wide variety of procedures, processes, and activities need to be validated, the field of validation is divided into a number of subsections including the following:

Process analytical technology (PAT) has been defined by the United States Food and Drug Administration (FDA) as a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of critical process parameters (CPP) which affect the critical quality attributes (CQA).

In drug development and medical device development the Investigator's Brochure (IB) is a comprehensive document summarizing the body of information about an investigational product obtained during a drug trial. The IB is a document of critical importance throughout the drug development process and is updated with new information as it becomes available. The purpose of the IB is to compile data relevant to studies of the IP in human subjects gathered during preclinical and other clinical trials.

Cleaning validation is the methodology used to assure that a cleaning process removes chemical and microbial residues of the active, inactive or detergent ingredients of the product manufactured in a piece of equipment, the cleaning aids utilized in the cleaning process and the microbial attributes. All residues are removed to predetermined levels to ensure the quality of the next product manufactured is not compromised by residues from the previous product and the quality of future products using the equipment, to prevent cross-contamination and as a good manufacturing practice requirement.

<span class="mw-page-title-main">Center for Drug Evaluation and Research</span> US Food and Drug Administration division

The Center for Drug Evaluation and Research is a division of the U.S. Food and Drug Administration (FDA) that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also legally considered drugs, but they are covered by the Center for Biologics Evaluation and Research. The center reviews applications for brand name, generic, and over the counter pharmaceuticals, manages US current Good Manufacturing Practice (cGMP) regulations for pharmaceutical manufacturing, determines which medications require a medical prescription, monitors advertising of approved medications, and collects and analyzes safety data about pharmaceuticals that are already on the market.

Drug Master File or DMF is a document prepared by a pharmaceutical manufacturer and submitted solely at its discretion to the appropriate regulatory authority in the intended drug market. There is no regulatory requirement to file a DMF. However, the document provides the regulatory authority with confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Typically, a drug master file is filed when two or more firms work in partnership on developing or manufacturing a drug product. The DMF filing allows a firm to protect its intellectual property from its partner while complying with regulatory requirements for disclosure of processing details.

Verification and validation are independent procedures that are used together for checking that a product, service, or system meets requirements and specifications and that it fulfills its intended purpose. These are critical components of a quality management system such as ISO 9000. The words "verification" and "validation" are sometimes preceded with "independent", indicating that the verification and validation is to be performed by a disinterested third party. "Integration verification and validation" can be abbreviated as "IV&V".

Clinical quality management systems (CQMS) are systems used in the life sciences sector designed to manage quality management best practices throughout clinical research and clinical study management. A CQMS system is designed to manage all of the documents, activities, tasks, processes, quality events, relationships, audits and training that must be administered and controlled throughout the life of a clinical trial. The premise of a CQMS is to bring together the activities led by two sectors of clinical research, Clinical Quality and Clinical Operations, to facilitate cross-functional activities to improve efficiencies and transparency and to encourage the use of risk mitigation and risk management practices at the clinical study level.

Safety pharmacology is a branch of pharmacology specialising in detecting and investigating potential undesirable pharmacodynamic effects of new chemical entities (NCEs) on physiological functions in relation to exposure in the therapeutic range and above.

The National Institute for Pharmaceutical Technology and Education (NIPTE) is a non-profit scientific and research and development organization that was established in 2005 and incorporated in June 2007 in the State of Indiana. Its offices are currently located in Minneapolis, Minnesota.

Regulated Product Submission (RPS) is a Health Level Seven (HL7) standard designed to facilitate the processing and review of regulated product information. RPS is being developed in response to performance goals that the U.S. Food and Drug Administration (FDA) is to achieve by 2012, as outlined in the Prescription Drug User Fee Act (PDUFA). In addition to the U.S., regulatory agencies from Europe, Canada, and Japan are at varying levels of interest and participation. Currently, the second release of RPS is in development.

<span class="mw-page-title-main">Drug packaging</span> Packaging for pharmaceutical preparations

Pharmaceutical packaging is the packages and the packaging processes for pharmaceutical preparations. It involves all of the operations from production through drug distribution channels to the end consumer.

Process validation is the analysis of data gathered throughout the design and manufacturing of a product in order to confirm that the process can reliably output products of a determined standard. Regulatory authorities like EMA and FDA have published guidelines relating to process validation. The purpose of process validation is to ensure varied inputs lead to consistent and high quality outputs. Process validation is an ongoing process that must be frequently adapted as manufacturing feedback is gathered. End-to-end validation of production processes is essential in determining product quality because quality cannot always be determined by finished-product inspection. Process validation can be broken down into 3 steps: process design, process qualification, and continued process verification.

<span class="mw-page-title-main">Arven Pharmaceuticals</span>

Arven Pharmaceuticals is a Turkish pharmaceutical corporation headquartered in Istanbul established as a subsidiary of Toksöz Group in 2013. Arven’s primary focus is development and production of high-technology inhaler and biotechnology products. The company is specialized on difficult to make products. Arven is the first Turkish company developing biosimilars for global markets, including the US and EU.

References

  1. 1 2 Juran, J.M. (1992). Juran on Quality by Design: The New Steps for Planning Quality into Goods and Services. Free Press.
  2. 1 2 Juran, J.M. (1986). "The Quality Trilogy: A Universal Approach to Managing for Quality". Quality Progress.
  3. ↑ Yu, Lawrence X. (2008). "Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control". Pharmaceutical Research. 25 (4): 781–791. doi:10.1007/s11095-007-9511-1. PMID   18185986. S2CID   11700550.
  4. ↑ Roadmap for implementation of quality by design (QbD) for biotechnology products
  5. ↑ Lebrun, Pierre; Govaerts, Bernadette; Debrus, Benjamin; Ceccato, Attilio; Caliaro, Gabriel; Hubert, Philippe; Boulanger, Bruno (2008). "Development of a new predictive modelling technique to find with confidence equivalence zone and design space of chromatographic analytical methods". Chemometrics and Intelligent Laboratory Systems. 91: 4–16. doi:10.1016/j.chemolab.2007.05.010. S2CID   124129813.
  6. ↑ Schweitzer, Mark; et al. (February 2010). "Implications and Opportunities of Applying QbD Principles to Analytical Measurements". Pharmaceutical Technology. 34 (2): 52–59.
  7. 1 2 3 4 5 DeFeo, Joseph A. & Juran, Joseph M. (2010). Juran's Quality Handbook: The Complete Guide to Performance Excellence 6/e. McGraw Hill.
  8. ↑ DeFeo, Joseph A. (2014). Juran's Quality Essentials for Leaders. McGraw Hill.
  9. 1 2 Early, John (14 Feb 2013). "Quality by Design, Part 1". Quality Digest.
  10. 1 2 Early, John (19 Feb 2013). "Quality by Design, Part 2". Quality Digest.
  11. ↑ Pharmaceutical Quality for the 21st Century: A Risk-Based Approach https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm128080.htm
  12. 1 2 "Process Validation: General Principles and Practices" (PDF). FDA Guidance. 2019-06-05.
  13. ↑ FDA Approves New Treatment for Diabetes 17 Oct 2006.
  14. ↑ "1st QBD Approval for Biologics: Gazyva Design Space". 2014-03-18.
  15. ↑ "PHARMACEUTICAL DEVELOPMENT Q8(R2)" (PDF).
  16. ↑ "QUALITY RISK MANAGEMENT Q9" (PDF).
  17. ↑ "PHARMACEUTICAL QUALITY SYSTEM Q10" (PDF).
  18. ↑ "DEVELOPMENT AND MANUFACTURE OF DRUG SUBSTANCES (CHEMICAL ENTITIES AND BIOTECHNOLOGICAL/BIOLOGICAL ENTITIES) Q11" (PDF).
  19. ↑ "TECHNICAL AND REGULATORY CONSIDERATIONS FOR PHARMACEUTICAL PRODUCT LIFECYCLE MANAGEMENT Q12" (PDF).
  20. ↑ "ICH Q13: Continuous Manufacturing of Drug Substances and Drug Products dated 14 November 2018" (PDF).
  21. ↑ "ICH Q14: Analytical Procedure Development and Revision of Q2(R1) Analytical Validation dated 14 November 2018" (PDF).
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